Abstract

3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) catalyzes the committed step in the biosynthesis of isoprenoids and steroids such as vitamin D and cholesterol. HMG-CoA reductase is the target of inhibitors, which present a first choice in cholesterol lowering medication. We have obtained well diffracting crystals of the catalytic domain of human HMG-CoS reductase. Although the structure of a homolog to mammalian HMG-CoA reductase from Pseudomonas mevalonii has been solved, the sequence identity to human reductase is only 20% and a molecular replacement solution has not yet been found. We intend to collect MAD data using seleno-methionine crystals to help solve the structure of the catalytic domain of human HMG-CoA reductase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-20
Application #
6119595
Study Section
Project Start
1999-03-01
Project End
2000-04-14
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Vickers, Chelsea; Liu, Feng; Abe, Kento et al. (2018) Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to ?-l-fucosidases from GH29. J Biol Chem 293:18296-18308
Nguyen, Phong T; Lai, Jeffrey Y; Lee, Allen T et al. (2018) Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter. Proc Natl Acad Sci U S A 115:E10596-E10604
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Herrera, Nadia; Maksaev, Grigory; Haswell, Elizabeth S et al. (2018) Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance. Sci Rep 8:14566
Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; Jönsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Feinberg, Hadar; Jégouzo, Sabine A F; Rex, Maximus J et al. (2017) Mechanism of pathogen recognition by human dectin-2. J Biol Chem 292:13402-13414
Warelow, Thomas P; Pushie, M Jake; Cotelesage, Julien J H et al. (2017) The active site structure and catalytic mechanism of arsenite oxidase. Sci Rep 7:1757

Showing the most recent 10 out of 604 publications